Compositions and Methods for Functionalized Patterning of Tissue Engineering Substrates Including Bioprinting Cell-Laden Constructs for Multicompartment Tissue Chambers

Abstract

The present invention relates to microfluidic systems and methods for monitoring or detecting a change in a characteristic of an input substance. Specifically, the invention relates to a model for in vitro pharmacokinetic study and other pharmaceutical applications, as well as other uses including computing, sensing, filtration, detoxification, production of chemicals and biomolecules, testing cell/tissue behavior, toxicology, drug metabolism, drug screening, drug discovery, and implantation into a subject. The present invention also relates to systems and methods of a microplasm functionalized surface patterning of a substrate. The present invention represents an improvement over existing plasma systems used to modify the surface of a substrate, as the present invention creates surface patterning without the use of a mask, stamp or a chemical treatment.

1 . A microfluidic system for monitoring or detecting a change in a characteristic of an input substance, the microfluidic system comprising:
 a cover platform having an inlet for delivery of an input substance and an outlet for removal of an output substance;   a substrate platform having a tissue chamber in a substrate body of the substrate platform and a three-dimensional tissue analog comprising cells mixed with a basement membrane matrix (BME);   a first microfluidic channel in fluid communication with the inlet for delivery of the input substance and the tissue chamber;   a second microfluidic channel in fluid communication with the outlet for removal of the output substance, provided that the substrate platform and the cover platform are superimposed to form a sealed assembly;   an input substance unit; and   an optional pumping assembly and detecting unit.   
     
     
         2 . The microfluidic system of  claim 1 , wherein the substrate platform comprises the first microfluidic channel and the second microfluidic channel in fluid communication with the tissue chamber. 
     
     
         3 . The microfluidic system of  claim 1 , wherein the cover platform comprises the first microfluidic channel and the second microfluidic channel in fluid communication with the tissue chamber. 
     
     
         4 . The microfluidic system of  claim 1 , wherein at least one of the cover platform and the substrate platform comprises a surface with an improved hydrophilicity. 
     
     
         5 . The microfluidic system of  claim 1 , wherein at least one of the cover platform and the substrate platform are made of a polymer, glass, a ceramic, a metal, an alloy, or a combination thereof. 
     
     
         6 . The microfluidic system of  claim 1 , wherein the cover platform is made of a plasma treated glass and the substrate platform is made of a plasma treated biologically-compatible polymer composed of a plurality of siloxane units. 
     
     
         7 . The microfluidic system of  claim 1 , wherein the tissue analog is at least one selected from the group consisting of heart, stomach, kidney, intestine, lung, liver, fat, bone, cartilage, skeletal muscle, smooth muscle, cardiac muscle, bone marrow, muscle, brain, and pancreas. 
     
     
         8 . The microfluidic system of  claim 1 , comprising a plurality of microfluidic channels. 
     
     
         9 . The microfluidic system of  claim 1 , comprising a plurality of tissue chambers. 
     
     
         10 . A method of monitoring or detecting a change in a characteristic of an input substance, the method comprising:
 providing the microfluidic system of  claim 1 ;   providing the input substance unit comprising the input substance;   directing the input substance into the microfluidic system, wherein the input substance flows through the inlet for delivery of the input substance and the first microfluidic channel into the tissue chamber having the tissue analog;   removing the output substance from the microfluidic system via the second microfluidic channel and the outlet for removal of the output substance;   obtaining at least a portion of the input substance prior to entry into the microfluidic system and at least a portion of the output substance after exiting the microfluidic system;   measuring the characteristic of the input substance prior to entry into the microfluidic system and measuring the characteristic of the output substance after exiting the microfluidic system; and   comparing the measured characteristic of the input substance prior to entry into the microfluidic system with the measured characteristic of the output substance after exiting the microfluidic system;   thereby monitoring or detecting a change in the characteristic of the input substance.   
     
     
         11 . The method of  claim 10 , wherein the input comprises a drug. 
     
     
         12 . The method of  claim 11 , wherein said monitoring or detecting the change in the characteristic of the input substance comprises:
 collecting the output comprising a metabolite having a detectable characteristic;   detecting the detectable characteristic; and   correlating the detectable characteristic to at least the extent and rate of metabolism of the input substance.   
     
     
         13 . A microplasma system for functionalized patterning of a tissue engineering substrate, the system comprising a microplasma nozzle fixed adjacent to a substrate material that is affixed to a platform moveable by a motion control system to position and move the platform in the X, Y and Z directions in relation to the fixed microplasma nozzle to create a functionalized pattern on the surface of the substrate material. 
     
     
         14 . The system of  claim 13 , wherein the substrate material is polycaprolactone. 
     
     
         15 . A microplasma system for functionalized patterning of a tissue engineering substrate, the system comprising a moveable microplasm nozzle affixed to motion control system to position and move the microplasma nozzle in the X, Y and Z directions in relation to a substrate material to create a functionalized pattern on the surface of the substrate material. 
     
     
         16 . The microplasm system of  claim 14 , wherein said microplasm nozzle is affixed to a multi-nozzle bioprinting system comprising:
 a data processing system that processes a designed scaffold model and converts it into a layered process tool path;   a motion control system driven by the layered process tool path; and   a material delivery system comprising multiple nozzles of different types;   wherein at least one of the nozzles deposits at least one substrate material, and at least one of the nozzles deposits at least one type of cell, and at least one of the nozzles deposits at least one biomolecule;   thereby constructing a scaffold having a microplasma functionalized pattern.   
     
     
         17 . The system of  claim 15 , wherein the substrate material is polycaprolactone. 
     
     
         18 . A method of creating a functionalized pattern on the surface of a tissue engineering substrate comprising the steps of:
 fixing a microplasma nozzle adjacent to a substrate material that is affixed to a platform moveable by a motion control system; and   moving the platform in the X, Y and Z directions in relation to the fixed microplasma nozzle to create a functionalized pattern on the surface of the substrate material.   
     
     
         19 . The method of  claim 18 , wherein the substrate material is polycaprolactone. 
     
     
         20 . A method of creating a functionalized pattern on the surface of a tissue engineering substrate comprising the step of moving a microplasm nozzle affixed to motion control system in the X, Y and Z directions in relation to a substrate material to create a functionalized pattern on the surface of the substrate material. 
     
     
         21 . The method of  claim 20 , wherein the microplasma nozzle is integrated into a multi-nozzle bioprinting system. 
     
     
         22 . The method of  claim 20 , wherein the substrate material is polycaprolactone.